title: Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses.
abstract: Since the beginning of the 20th century, humans have experienced four influenza pandemics, including the devastating 1918 'Spanish influenza'. Moreover, H5N1 highly pathogenic avian influenza (HPAI) viruses are currently spreading worldwide, although they are not yet efficiently transmitted among humans. While the threat of a global pandemic involving a highly pathogenic influenza virus strain looms large, our mechanisms to address such a catastrophe remain limited. Here, we show that pre-stimulation of Toll-like receptors (TLRs) 2 and 4 increased resistance against influenza viruses known to induce high pathogenicity in animal models. Our data emphasize the complexity of the host response against different influenza viruses, and suggest that TLR agonists might be utilized to protect against lethality associated with highly pathogenic influenza virus infection in humans.
authors.affiliation: Department of Microbiology and Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan. kyoko.tanaka@aioros.ocn.ne.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinya
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamura
authors.forename: Setsuko
authors.initials: S
authors.lastname: Sueta
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasai
authors.forename: Motoko
authors.initials: M
authors.lastname: Tanaka
authors.forename: Teridah E
authors.initials: TE
authors.lastname: Ginting
authors.forename: Akiko
authors.initials: A
authors.lastname: Makino
authors.forename: Amie J
authors.initials: AJ
authors.lastname: Eisfeld
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014774:Virulence
chemical_list: D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4